BASICS OF REACTION MECHANISM - Gneet of reaction mechanism.pdfCHEMSITRY NOTES 3
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Cannizzaro Reaction
Part I
Cannizzaro Reaction
In the presence of concentrated alkali , aldehydes
containing no α - hydrogens undergo self oxidation
& reduction (Redox) reaction to yield a mixture of
an alcohol & a salt of carboxylic acid.
R C
O
H2OH
-
concentratedR C
O
O R C
OH
H
Hcarboxylate
anion alcohol
Examples:
C
O
H HCCH3C
O
H
H3C
H3C
CCH3C
O
H
H3C
HO
Benzaldehyde
2,2-Dimethylpropanal
Formaldehyde
( Methanal )
2-Hydroxy-2-methylpropanal
C
O
R H
Aldehyde
C
O
H
Mechanism of the reaction
1st Mechanism:
Three proposed mechanisms,
Nucleophilic addition of an OH - ion to the 1st
aldehyde molecule gives a tetrahedral intermediate I .
Step I
R C
O
H OH C
O
RH
OH
Tetrahedral intermediate
intermediate I
carbonyl-hydroxide
anion
aldehyde-hydroxide
adduct1st aldehyde
molecule
conc.
alkali
Step II Hydride shift: The tetrahedral intermediate I
, expels a hydride ion* as a leaving group** and is
thereby oxidized. A second aldehyde molecule accepts
the hydride ion in another nucleophilic addition step
and is thereby reduced.
R C
O
H C
O
RH
OH
CR
O
HH
C
O
OHR
CR
OH
HH
C
O
OR
2nd aldehyde
moleculeintermediate I
salt of
carboxylic acidalcohol
Mechanism : nd2
Step I Generation of the Intermediate I; Nucleophilic
addition of OH - ion to an aldehyde molecule to give
a carbonyl–hydroxide anion (intermediate I) as in the
1st mechanism.
Notes :
* A hydride ion is the anion of hydrogen , H −, have
nucleophilic, reducing or basic properties.
** The strong electron – donating character of O –
greatly facilitate the ability of the aldehydic
hydrogen to leave with it's electron pair .
A hydride ion from one carbonyl – hydroxide
anion ( I ) is added to another carbonyl – hydroxide
anion ( I ).
In the last step , the alkoxide anion receives a proton
from the carboxylic acid.
The acid can be recovered by acidifying the mixture.
Step II
R C
OH
H
O
R C
OH
H
O
R C
OH
O
R C O
H
HOH
R C
H
H
OHR C
O
O
intermediate I intermediate I
Mechanism : rd3
Step I Nucleophilic addition to give intermediate I
as in the 1st mechanism.
Step II Deprotonation of the intermediate I to give
a dianion intermediate II.
R C
O
O
H + OH
H
R C
O
H
O
H2O
intermediate II
(doubly-charged anion)intermediate I
The unstable intermediate II releases a
hydride anion which attacks another molecule of the
aldehyde. In this process the dianion intermediate
converts to a carboxylate anion and the aldehyde to
an alkoxide anion.
Step III
The alkoxide anion then picks up a proton from
water to provide the alcohol final product ¤ , while the
carboxylate anion is converted to the carboxylic acid
product after acid work-up ¤¤.
¤ The alkoxide anion is more basic than water, so it
can pick up a proton from water. ¤¤ The carboxylate anion is less basic than water ,
thus it can not pick up a proton from water and
require an acid work up to protonate .
R C
O
H
H+ R C
O
HR C
O
H
O
R C
O
O
+
intermediate II another aldehyde
molecule
alkoxide
anion
carboxylate
anion
H2OOH
R C
O
O
R C
OH
H
H+
How can you prove that the hydrogen comes from
another equivalent of aldehyde and not from the
medium , ( i.e. Involvement of a hydride shift in the
mechanism of Cannizzaro reaction ) ? Solution:
When the reaction was run in D2O instead of H2O, the recovered
alcohol contained no α deuterium .
Crossed Cannizzaro Reaction
In general, a mixture of aldehydes undergoes a
Cannizzaro reaction to yield all possible products .
If one of the aldehydes is formaldehyde, the reaction
yields almost exclusively salt of formic acid and the
alcohol corresponding to the other aldehyde. Such a
reaction is called a Crossed Cannizzaro Reaction .
R C
O
H
OH -
R C
OH
H
H
alcohol
H C
O
H H C
O
O
formate
anionformaldehyde
Aldol Condensation
Aldehydes or ketones with an α – hydrogen ( acidic * )
undergo Aldol Condensation (carbonyl condensation
reaction ) under the influence of dilute base or acid,
2 molecules of aldehyde or ketone combine to form
a β - hydroxy aldehyde or β - hydroxy ketone in such
a way that the α - carbon of the 1st becomes attached
to the carbonyl carbon of the 2nd.
H3C C
O
H C C
O
H
H
H
H
Acetaldehyde Acetaldehyde
H3C C
OH
C
H
H
H
C
O
H
OH -
3- Hydroxybutanal
* Two factors – one inductive , the other resonance – combine to make an hydrogen of an aldehyde or ketone relatively acidic.
The electron – withdrawing inductive effect of the carbonyl group increases the positive character of the -H, & resonance stabilizes the conjugate base.
The resonance of the conjugate base of an aldehyde or ketone is called an enolate ion . Of the two resonance structures shown for the conjugate base, the major contributor is the one with the negative charge on oxygen.
CC
H
O
CC
O
CC
O
Electron delocalization
stabilizes conjugate base Inductive effect increase
positive character of hydrogen
δ +
Synthesis of Benzoic acid and Benzyl alcohol
Benzaldehyde , C7H6O , ( C6H5CHO )
Molar mass = 106.12 g mol−1.
It's a colorless or yellowish liquid.
It has a characteristic pleasant almond - like odor .
Benzoic acid, C7H6O2 , ( C6H5COOH )
Molar mass = 122.12 g mol−1 .
Melting point = 121 – 123 oC.
It is a colorless plate or needle like crystals with a faint, pleasant odor.
Sparingly soluble in water but soluble in hot or boiled water.
Reacts with sodium bicarbonate to give CO2 gas.
Benzoic acid and it's salts are used as food preservatives.
Also used externally in the form of lotions , ointments ( e.g.
Whitfield ointment), mouth washes, etc.
Benzyl alcohol , C7H8O , ( C6H5CH2OH )
Molar mass =108.14 g mol−1.
Boiling point = 204 – 207 o C.
It is a colorless oily liquid with a mild pleasant aromatic odor,
immiscible with water and completely miscible with alcohols and
organic solvents as diethyl ether . It's a useful solvent due to its
polarity , low toxicity and low vapor pressure ( volatile with
steam ). It has some local anesthetic properties so it is useful as
an antipruretic and it is included in some dental remedies &
injectibles . Used in pharmaceutical preparations for local
application up to 10% in ointments as antipruretic and antiseptic.
Benzyl alcohol can be prepared by hydrolysis of
benzyl chloride with NaOH .
CH2Cl CH2OHOH
-
Benzoic acid can be prepared by the oxidation of
toluene.
CH3 COOH[ O ]
, both Benzoic acid & Benzyl alcohol can be However
prepared in the laboratory by Cannizzaro Reaction
, by the action of concentrated NaOH or KOH on
benzaldehyde.
C
O
H C
O
H C
O
O KKOH
C
H
OH
HPotassium benzoate Benzyl alcohol
Benzaldehyde Benzaldehyde
conce.
Name of Experiment : Cannizzaro Reaction. Aim of Experiment : Synthesis of Benzoic acid and Benzyl alcohol
Procedure:
1- Dissolve 7.2 g of KOH in about 7 ml of H2O
contained in a beaker.
2- Cool the solution to about 20 oC in an ice-water
bath.
3- Pour the solution into a 125 ml reagent bottle.
4- Add 7.3 ml of pure benzaldehyde , cork the bottle
securely and shake the mixture vigorously until it
has been converted to a thick emulsion.
5- Allow the mixture to stand overnight ( in this case
until the next laboratory period ) . By which time
the reaction should have been completed.
1- How would propanal react with KOH solution
under the condition of this experiment ?
Answer the same question for the reaction of
2,2-dimethylpropanal.
2- Write an equation for the reaction of a mixture of
benzaldehyde and 2,2-dimethylpropanal with
concentrated KOH solution . Show all possible
products.
3- Write a mechanism for the reaction of benzaldehy-
de with formaldehyde under strong basic conditions.
4- Complete the following reaction
C
O
HHconcentrated
KOHC
O
HH+
5- When o-phthalaldehyde is treated with base ,
o- (hydroxymethyl) benzoic acid is formed.
Show the mechanism of this reaction.
CHO
CHO
CO2H
CH2OH
1. - OH
2. H3O +
o-Phthalaldehyde o-(Hydroxymethyl)
benzoic acid
6- In the case of some aldehydes there is evidence that
intermediate II is the hydride donor in the Cannizz-
aro reaction.
a- How would II be formed from I ?
b- Why would you expect II to be a better hydride donor
than I ? ( Hint : What is one product of the hydride
transfer from II ? ) .
ArCHO
HCHO
(CH3)3CCHO
ArCOAr
ArCOCR3
No reaction Why??dilute OH
-
7- Explain ,
8- Find the most acidic H in tert-Butyl methyl ketone
& write a chemical equation for the proton-transfer
process that occurs on reaction with hydroxide ion.
C
O
CH3C
CH3
CH3
CH3
tert-Butyl methyl ketone
* Samira Finjan Hassan, Amer Nadem, May Mohammed
Jawad , A Laboratory manual on Practical Medical
Chemistry for 4th year students, University of Baghdad
, College of Pharmacy , Department of Pharmaceutical
Chemistry, 2010.
* Robert T. Morrison , Robert N. Boyd: “ Aldehydes and
Ketones” . Organic Chemistry, (6th) edition , Prentice -
Hall Inc.
* Carey, Francis A.: “Aldehydes and Ketones: Nucleophilic
Addition to the Carbonyl Group ” . Organic Chemistry
(6th) edition, McGraw-Hill companies, Inc.
* Vogel, Arthur,Textbook of Organic Chemistry,4th edition.
* John E. McMurry, Organic Chemistry, 8th edition, 2012